Gamma interferon (IFNgamma) is an essential cytokine for mediation of functions that are obligatory for good health, particularly that mediated through or maintained through CD4 T helper1 (Th1) cells. Further, IFNgamma possesses direct antiviral and anticellular (antitumor) activity. Thus, the development of IFNgamma mimetics has important implications for immune therapy in infectious diseases and cancer. The Specific Aims listed below directly test both the rational development of such mimetics as well as their use in the mediation of IFNgamma activity. 1. Synthesis of IFNgamma peptide mimetics based on sequence and structural similarity to biologically active IFNgamma C-terminal peptides. 2. Compare several methods for delivery of IFNgamma peptides intracellularly, including chemical modification and use of molecular expression systems. 3. Determine signaling function of IFNgamma peptide mimetics in terms of JAK/STAT activation, upregulation of tumor suppressor gene p21WAF/CIP, and down regulation of neu/HER-2protooncogene in cancer cells. 4. Determine cellular function of IFN? peptide mimetics in terms of antiviral activity, anticellular (antitumor) activity, and upregulation of MHC class II molecules. 5. Determine biological activity of IFNgamma mimetic peptides in mouse models of virus infection and cancer.